Results: Nonresponders to CBT or VEN, in contrast to responders, exhibited pretreatment hypermetabolism at the interface of the pregenual and subgenual cingulate cortices.

Limitations: Limitations of our study include the small sample sizes and the absence of both arterial sampling to determine absolute glucose metabolism and high-resolution structural magnetic resonance imaging coregistration for region-of-interest analyses.

Conclusions: Our current findings are consistent with those reported in previous studies of relative hyperactivity in the ventral anterior cingulate cortex in treatment-resistant populations.

Acknowledgements: We thank Doug Hussey, BSc; Alvina Ng, BSc; and Alan A. Wilson, PhD, from the PET Centre, University of Toronto. This study was supported by the Canadian Institutes of Health Research (# 86023 H.S.M., S.H.K., Z.V.S.) and Wyeth Pharmaceuticals (S.H.K., H.S.M., Z.V.S.).

Competing interests: This study was supported by the Canadian Institutes of Health Research and Wyeth Pharmaceuticals. None declared for Mr. Konarski and Drs. Segal, Lau and Bieling. Dr. Kennedy has conducted paid consultancies for Pfizer, Servier and Wyeth; received research support from ANS, AstraZeneca, CIHR, Eli Lilly, GlaxoSmithKline, Lundbeck, NARSAD, OMHF, OPGRS and the Stanley Foundation; and has received speaker fees from ANS, Astra- Zeneca, Biovail, Eli Lilly, Lundbeck, Servier and Wyeth. Dr. McIntyre sits on the advisory boards of AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen-Ortho, Solvay/Wyeth, Eli Lilly, Organon, Lundbeck, Biovail, Pfizer and Shire; he has received speaker fees from Janssen-Ortho, AstraZeneca, Eli Lilly, Lundbeck and Biovail and research support from Eli Lilly. Dr. Mayberg has consulted for Advanced Neuromodulation Systems Inc.

Contributors: Drs. Mayberg, Kennedy and Segal designed the study. Mr. Konarski and Drs. Segal, Lau, Bieling and Mayberg acquired the data. Mr. Konarski and Drs. Kennedy and Mayberg analyzed the data. Mr. Konarski and Drs. Kennedy and McIntyre wrote the paper. Mr. Konarski and Drs. Kennedy, Segal, Lau, Bieling, McIntyre and Mayberg reviewed the article. All authors approved final publication.